International Journal of Cardiology 177 (2014) 136–138
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the editor
Long term followup of aortic root size after repair of tetralogy of Fallot Mark Dennis a,b,⁎, Maarit Laarkson c, Ratnasari Padang a,b, David J. Tanous d, Peter Robinson d, Lynne Pressley b, Shamus O'Meagher b, David Celermajer a,b, Rajesh Puranik a,b,e a
Sydney Medical School, University of Sydney, Sydney, Australia Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Prince of Wales Clinical School, University of New South Wales, Sydney, Australia d Department of Cardiology, Westmead Hospital, Sydney, Australia e SMRI Imaging, RPAH Medical Centre, Sydney, Australia b c
a r t i c l e
i n f o
Article history: Received 10 September 2014 Accepted 20 September 2014 Available online 28 September 2014 Keywords: Tetralogy of Fallot Aortic root Aortic dilatation Magnetic resonance imaging MRI
Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart defect. Pulmonary atresia with ventricular septal defect (PA VSD) is a severe form of tetralogy of Fallot with complete obstruction of the pulmonary artery resulting in diversion of all blood from the right ventricle into the aorta. Early detection of these disorders and subsequent corrective surgery has improved long-term prognosis and overall survival. Progressive aortic root dilatation is a well-known in patients with repaired ToF with a prevalence between 15% and 87% depending on the criteria used [1–3]. Abnormal haemodynamics with increased aortic flow due to right to left shunting prior to definitive repair coupled with underlying histological changes including, medionecrosis and loss of elastic lamellae within the aortic root, are thought to contribute to this dilatation [4]. Increased arterial wall stiffness has also been observed in patients with late aortic root dilatation after tetralogy repair [5]. Aortic root dilatation has led to concerns over the development of significant aortic regurgitation and aortic dissection. Therefore, understanding the prevalence of dilatation among patients with repaired ToF and associated risk factors is important in risk stratification, monitoring and timing of possible surgical intervention. ⁎ Corresponding author at: Cardiology Department, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia. Tel.: +61 2 9515 6111, +61 400701265(mob); fax: +61 2 9519 4938. E-mail address: [email protected] (M. Dennis).
http://dx.doi.org/10.1016/j.ijcard.2014.09.113 0167-5273/Crown Copyright © 2014 Published by Elsevier Ireland Ltd. All rights reserved.
We conducted a single centre retrospective review of 95 patients, aged 16 years and over with repaired either ToF or PA VSD who were referred to Royal Prince Alfred cardiac MRI (cMRI) centre between 2008 and 2013 inclusive. We analysed the prevalence of and possible risk factors for development of aortic root dilatation, measured using cardiac magnetic resonance imaging as defined by an absolute value of ≥ 40 mm measured at the sinus of Valsalva. The Human Research Ethics Committee (HREC) approved the study. Of the 95 patients, 85 (89%) had surgically repaired ToF and 11% had PA VSD (Table 1). The mean age of the cohort was 36 ± 5.5 years. Aortic root dilatation (≥40 mm) was observed in 23% (22) of patients, 4% had an aortic diameter N45 mm. The mean age of the dilated group was 44 ± 4.1 years, compared to the non-dilated group 34 ± 3.7 years. In univariate analysis male sex, larger body surface area, left ventricular ejection fraction, net forward aortic flow, and pulmonary regurgitation fraction were associated with a dilated aortic root. After adjusting for age and sex (Table 2) only male sex (OR = 7.54, CI: 1.97, 28.8; p = 0.003) and older age at correction (OR = 1.21, CI: 1.00, 1.47; p = 0.05) were associated with dilatation. No patients had significant aortic regurgitation or dissection. This study confirms that a significant proportion of adult patients with repaired ToF have aortic root dilatation consistent with the largest previous study using the same dilatation criteria [3]. PA VSD variant, right aortic arch and time since surgical correction have all variably been associated with dilatation in patients with repaired ToF [2,3]. After adjusting for age and sex, male sex and age at surgical correction were significantly associated factors for aortic dilatation in our study. Aortic size in normal patients is affected by body surface area, age and sex [3,6] with male sex being the most consistent factor. Males with congenital heart disease have also been shown to have an increased risk of aortic aneurysms, dissections and have a higher probability of requiring surgery when compared to females [7]. Why these gender-based differences exist is unclear and is complicated by the fact that the underlying pathophysiological mechanism for aortic root dilatation is still to be elucidated. Gender may play a role in decreasing distensibility/increasing arterial stiffness and therefore dilatation. Females have been shown to have higher aortic stiffness pre-puberty and post menopause [8], however young women may have more distensible arteries than similarly aged men. Sex steroid differences between genders have been postulated to contribute to these differences [8].
M. Dennis et al. / International Journal of Cardiology 177 (2014) 136–138
137
Table 1 Baseline characteristics according to aortic root diameter (N = 95). Variablea
Aortic root diameter at sinus of Valsalva ≥40 mm (N = 22)
Pb
b40 mm (N = 73)
Demographics Age at correction Time since correction PA VSD Male Body surface area (BSA; m2) Right aortic arch Aberrant neck vesselsc
2.6 (1.1, 4.3)
1.8 (1.1, 3.5)
0.45
24.2 (18.5, 28.8) 2 (9) 18 (82) 1.9 (1.8, 2.1) 8 (36) 1 (6)
20.4 (17.3, 25.8) 8 (11) 34 (47) 1.8 (1.6, 1.9) 16 (22) 11 (17)
0.11 0.31 0.004 0.004 0.17 0.17
Ventricular volume measurements Left ventricular stroke volumed Right ventricular stroke volumed Left ejection fractiond Right ejection fractiond Left cardiac outputd Right cardiac outputd
90 (81, 99) 118 (90, 158) 55 (52, 59) 50 (45, 54) 5.6 (5.2, 6.4) 7.6 (5.9, 10.5)
79 (68, 94) 126 (97, 147) 58 (54, 65) 50 (45, 57) 5.8 (4.7, 6.8) 8.3 (6.7, 11.1)
0.04 0.75 0.03 0.38 0.50 0.32
Great vessel flow Net forward flow aortae Net forward flow mpae Pulmonary regurgitation volumef Pulmonary regurgitation fraction%g
86.5 (75.5, 92.5) 87.5 (75, 93) 17.5 (6.0, 58.0) 17.0 (6.6, 39.5)
76 (65,88) 74 (64, 86) 38.0 (12.5, 59.0) 34.1 (13.0, 42.4)
0.02 0.03 0.19 0.05
a
Continuous variables presented as median and interquartile range (25th, 75th percentile) and categorical variables as n (%). Based on non-parametric Wilcoxon rank-sum test (continuous variables), chi-square test (categorical variables with all expected cell frequencies ≥ 5), or Fisher exact test (categorical variables with any of the expected cell frequencies b 5). c N = 83. d N = 94. e N = 89. f N = 88. g N = 90. b
Our study is one of the few that has used cMRI to review right ventricular (RV) and left ventricular (LV) parameters and aortic root dilatation. After adjusting for age and sex, neither LV nor RV flow nor volume measurements had a significant association with the aortic root dilatation. The absence of an association in our study may support the theory that the contribution of altered haemodynamics to aortic root dilatation occurs before surgical correction and the impact after correction is less significant. Concerns over aortic root dilatation in repaired ToF patients have centred on the possible development of significant aortic regurgitation and dissection. Whilst our study has demonstrated that a significant
proportion of repaired tetralogy of Fallot aortas is dilated, the prevalence of significant aortic regurgitation is less than previous studies, where moderate to severe aortic regurgitation was reported in up to 15% of patients [9]. There were no cases of aortic dissection in our cohort which supports existing evidence that these events are very rare and limited to case reports. Despite this low relative risk of aortic dilatation in repaired ToF patients, its presence may still be important in future surgical decisions. cMRI is uniquely placed to monitor both extent of pulmonary regurgitation and aortic root dilatation. The extent, rate, and likelihood of aortic root dilatation based on established risk factors such as age and gender
Table 2 Factors associated with a dilated aortic root, defined by aortic root diameter at sinus of Valsalva ≥ 40 mm (N = 95). Variable
Univariate model
Age- and sex-adjusted model
OR
(95% CI)
P
OR
(95% CI)
P
1.11 1.04 0.81 5.16 14.6 2.04 0.29
(0.96, 1.28) (0.98, 1.10) (0.16, 4.14) (1.59, 16.7) (2.22, 96.3) (0.73, 5.71) (0.04, 2.40)
0.16 0.20 0.80 0.006 0.005 0.18 0.25
1.21 1.05 0.50 7.54 6.62 1.66 0.24
(1.00, 1.47) (0.97, 1.13) (0.08, 3.10) (1.97, 28.8) (0.81, 53.9) (0.54, 5.08) (0.03, 2.07)
0.05 0.25 0.45 0.003 0.08 0.37 0.19
Absolute ventricular volume measurements Left ventricular stroke volume Right ventricular stroke volume Left ejection fraction Right ejection fraction Left cardiac output Right cardiac output
1.02 1.00 0.92 0.97 1.09 0.91
(1.00, 1.05) (0.98, 1.01) (0.85, 0.99) (0.91, 1.03) (0.81, 1.47) (0.78, 1.07)
0.07 0.71 0.03 0.30 0.57 0.25
1.01 0.99 0.95 0.99 0.96 0.87
(0.99, 1.04) (0.98, 1.01) (0.87, 1.03) (0.93, 1.05) (0.69, 1.33) (0.72, 1.05)
0.37 0.43 0.19 0.72 0.80 0.15
Great vessel flow Net forward flow aorta Net forward flow mpa Pulmonary regurgitation volume Pulmonary regurgitation volume %
1.03 1.03 0.99 0.97
(1.00, 1.06) (1.00, 1.06) (0.97, 1.01) (0.94, 1.00)
0.04 0.04 0.15 0.04
1.02 1.02 0.99 0.98
(0.99, 1.05) (0.99, 1.05) (0.97, 1.01) (0.95, 1.01)
0.25 0.26 0.22 0.11
Age at correction, per year Time since correction, per year PA VSD Male Body surface area (BSA), per m2 Right aortic arch Aberrant neck vessels
138
M. Dennis et al. / International Journal of Cardiology 177 (2014) 136–138
should be taken into account when determining the timing of pulmonary valve replacement in repaired ToF. It is acknowledged that our study maybe influenced by selection and survivor bias with only “survivors” referred to our tertiary referral centre being studied. In our own review of unexpected deaths of adult with ToF, none were attributable to aortic disease after comprehensive postmortem examination [10]. In conclusion our study adds to the growing body of research that identifies that, whilst aortic root dilatation in patients with repaired tetralogy of Fallot does occur, the risk of serious complications including aortic regurgitation and aortic dissection is low. The optimal timing and need for intervention on a dilated aortic root in these patients is still not clear. It also confirms that male sex is the only consistent significant factor contributing to aortic root dilatation and should be taken into account in surveillance of these patients. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] Niwa K, Siu SC, Webb GD, Gatzoulis MA. Progressive aortic root dilatation in adults late after repair of tetralogy of Fallot. Circulation 2002;106:1374–8.
[2] Chong WY, Wong WH, Chiu CS, Cheung YF. Aortic root dilation and aortic elastic properties in children after repair of tetralogy of Fallot. Am J Cardiol 2006;97:905–9. [3] Mongeon FP, Gurvitz MZ, Broberg CS, Aboulhosn J, Opotowsky AR, Kay JD, et al. Aortic root dilatation in adults with surgically repaired tetralogy of Fallot, a multi center cross-sectional study. Circulation 2013;127:172–9. [4] Chowdhury UK, Mishra AK, Ray R, Kalaivani M, Reddy SM, Venugopal P. Histopathologic changes in ascending aorta and risk factors related to histopathologic conditions and aortic dilatation in patients with tetralogy of Fallot. J Thorac Cardiovasc Surg 2008;135:69–77. [5] Senzaki H, Iwamoto Y, Ishido H, Matsunaga T, Taketazu M, Kobayashi T, et al. Arterial haemodynamics in patients after repair of tetralogy of Fallot: influence on left ventricular after load and aortic dilatation. Heart 2008;94:70–4. [6] Devereux RB, de Simone G, Arnett DK, Best LG, Boerwinkle E, Howard BV, et al. Normal limits in relation to age, body size and gender of two-dimensional echocardiographic aortic root dimensions in persons ≥15 years of age. Am J Cardiol 2012; 110:1189–94. [7] Verheught CL, Uiterwaal CS. Gender and outcome in congenital heart disease. Circulation 2008;118:26–32. [8] Rossi P, Frances Y, Kingwell B, Ahimastos A. Gender differences in artery wall biomechanical properties throughout life. J Hypertens 2011;29:1023–33. [9] Niwa K. Aortic root dilatation in tetralogy of Fallot long-term after repair — histology of the aorta in tetralogy of Fallot: evidence of intrinsic aortopathy. Int J Cardiol 2005; 103:117–9. [10] O'Meagher S, Choudhary P, Duflou J, Puranik R, Celermajer D. Causes of death in tetralogy of Fallot in adults — an autopsy study. Int J Cardiol 2013;168(2013):1547–8.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the editor
Long term followup of aortic root size after repair of tetralogy of Fallot Mark Dennis a,b,⁎, Maarit Laarkson c, Ratnasari Padang a,b, David J. Tanous d, Peter Robinson d, Lynne Pressley b, Shamus O'Meagher b, David Celermajer a,b, Rajesh Puranik a,b,e a
Sydney Medical School, University of Sydney, Sydney, Australia Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Prince of Wales Clinical School, University of New South Wales, Sydney, Australia d Department of Cardiology, Westmead Hospital, Sydney, Australia e SMRI Imaging, RPAH Medical Centre, Sydney, Australia b c
a r t i c l e
i n f o
Article history: Received 10 September 2014 Accepted 20 September 2014 Available online 28 September 2014 Keywords: Tetralogy of Fallot Aortic root Aortic dilatation Magnetic resonance imaging MRI
Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart defect. Pulmonary atresia with ventricular septal defect (PA VSD) is a severe form of tetralogy of Fallot with complete obstruction of the pulmonary artery resulting in diversion of all blood from the right ventricle into the aorta. Early detection of these disorders and subsequent corrective surgery has improved long-term prognosis and overall survival. Progressive aortic root dilatation is a well-known in patients with repaired ToF with a prevalence between 15% and 87% depending on the criteria used [1–3]. Abnormal haemodynamics with increased aortic flow due to right to left shunting prior to definitive repair coupled with underlying histological changes including, medionecrosis and loss of elastic lamellae within the aortic root, are thought to contribute to this dilatation [4]. Increased arterial wall stiffness has also been observed in patients with late aortic root dilatation after tetralogy repair [5]. Aortic root dilatation has led to concerns over the development of significant aortic regurgitation and aortic dissection. Therefore, understanding the prevalence of dilatation among patients with repaired ToF and associated risk factors is important in risk stratification, monitoring and timing of possible surgical intervention. ⁎ Corresponding author at: Cardiology Department, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia. Tel.: +61 2 9515 6111, +61 400701265(mob); fax: +61 2 9519 4938. E-mail address: [email protected] (M. Dennis).
http://dx.doi.org/10.1016/j.ijcard.2014.09.113 0167-5273/Crown Copyright © 2014 Published by Elsevier Ireland Ltd. All rights reserved.
We conducted a single centre retrospective review of 95 patients, aged 16 years and over with repaired either ToF or PA VSD who were referred to Royal Prince Alfred cardiac MRI (cMRI) centre between 2008 and 2013 inclusive. We analysed the prevalence of and possible risk factors for development of aortic root dilatation, measured using cardiac magnetic resonance imaging as defined by an absolute value of ≥ 40 mm measured at the sinus of Valsalva. The Human Research Ethics Committee (HREC) approved the study. Of the 95 patients, 85 (89%) had surgically repaired ToF and 11% had PA VSD (Table 1). The mean age of the cohort was 36 ± 5.5 years. Aortic root dilatation (≥40 mm) was observed in 23% (22) of patients, 4% had an aortic diameter N45 mm. The mean age of the dilated group was 44 ± 4.1 years, compared to the non-dilated group 34 ± 3.7 years. In univariate analysis male sex, larger body surface area, left ventricular ejection fraction, net forward aortic flow, and pulmonary regurgitation fraction were associated with a dilated aortic root. After adjusting for age and sex (Table 2) only male sex (OR = 7.54, CI: 1.97, 28.8; p = 0.003) and older age at correction (OR = 1.21, CI: 1.00, 1.47; p = 0.05) were associated with dilatation. No patients had significant aortic regurgitation or dissection. This study confirms that a significant proportion of adult patients with repaired ToF have aortic root dilatation consistent with the largest previous study using the same dilatation criteria [3]. PA VSD variant, right aortic arch and time since surgical correction have all variably been associated with dilatation in patients with repaired ToF [2,3]. After adjusting for age and sex, male sex and age at surgical correction were significantly associated factors for aortic dilatation in our study. Aortic size in normal patients is affected by body surface area, age and sex [3,6] with male sex being the most consistent factor. Males with congenital heart disease have also been shown to have an increased risk of aortic aneurysms, dissections and have a higher probability of requiring surgery when compared to females [7]. Why these gender-based differences exist is unclear and is complicated by the fact that the underlying pathophysiological mechanism for aortic root dilatation is still to be elucidated. Gender may play a role in decreasing distensibility/increasing arterial stiffness and therefore dilatation. Females have been shown to have higher aortic stiffness pre-puberty and post menopause [8], however young women may have more distensible arteries than similarly aged men. Sex steroid differences between genders have been postulated to contribute to these differences [8].
M. Dennis et al. / International Journal of Cardiology 177 (2014) 136–138
137
Table 1 Baseline characteristics according to aortic root diameter (N = 95). Variablea
Aortic root diameter at sinus of Valsalva ≥40 mm (N = 22)
Pb
b40 mm (N = 73)
Demographics Age at correction Time since correction PA VSD Male Body surface area (BSA; m2) Right aortic arch Aberrant neck vesselsc
2.6 (1.1, 4.3)
1.8 (1.1, 3.5)
0.45
24.2 (18.5, 28.8) 2 (9) 18 (82) 1.9 (1.8, 2.1) 8 (36) 1 (6)
20.4 (17.3, 25.8) 8 (11) 34 (47) 1.8 (1.6, 1.9) 16 (22) 11 (17)
0.11 0.31 0.004 0.004 0.17 0.17
Ventricular volume measurements Left ventricular stroke volumed Right ventricular stroke volumed Left ejection fractiond Right ejection fractiond Left cardiac outputd Right cardiac outputd
90 (81, 99) 118 (90, 158) 55 (52, 59) 50 (45, 54) 5.6 (5.2, 6.4) 7.6 (5.9, 10.5)
79 (68, 94) 126 (97, 147) 58 (54, 65) 50 (45, 57) 5.8 (4.7, 6.8) 8.3 (6.7, 11.1)
0.04 0.75 0.03 0.38 0.50 0.32
Great vessel flow Net forward flow aortae Net forward flow mpae Pulmonary regurgitation volumef Pulmonary regurgitation fraction%g
86.5 (75.5, 92.5) 87.5 (75, 93) 17.5 (6.0, 58.0) 17.0 (6.6, 39.5)
76 (65,88) 74 (64, 86) 38.0 (12.5, 59.0) 34.1 (13.0, 42.4)
0.02 0.03 0.19 0.05
a
Continuous variables presented as median and interquartile range (25th, 75th percentile) and categorical variables as n (%). Based on non-parametric Wilcoxon rank-sum test (continuous variables), chi-square test (categorical variables with all expected cell frequencies ≥ 5), or Fisher exact test (categorical variables with any of the expected cell frequencies b 5). c N = 83. d N = 94. e N = 89. f N = 88. g N = 90. b
Our study is one of the few that has used cMRI to review right ventricular (RV) and left ventricular (LV) parameters and aortic root dilatation. After adjusting for age and sex, neither LV nor RV flow nor volume measurements had a significant association with the aortic root dilatation. The absence of an association in our study may support the theory that the contribution of altered haemodynamics to aortic root dilatation occurs before surgical correction and the impact after correction is less significant. Concerns over aortic root dilatation in repaired ToF patients have centred on the possible development of significant aortic regurgitation and dissection. Whilst our study has demonstrated that a significant
proportion of repaired tetralogy of Fallot aortas is dilated, the prevalence of significant aortic regurgitation is less than previous studies, where moderate to severe aortic regurgitation was reported in up to 15% of patients [9]. There were no cases of aortic dissection in our cohort which supports existing evidence that these events are very rare and limited to case reports. Despite this low relative risk of aortic dilatation in repaired ToF patients, its presence may still be important in future surgical decisions. cMRI is uniquely placed to monitor both extent of pulmonary regurgitation and aortic root dilatation. The extent, rate, and likelihood of aortic root dilatation based on established risk factors such as age and gender
Table 2 Factors associated with a dilated aortic root, defined by aortic root diameter at sinus of Valsalva ≥ 40 mm (N = 95). Variable
Univariate model
Age- and sex-adjusted model
OR
(95% CI)
P
OR
(95% CI)
P
1.11 1.04 0.81 5.16 14.6 2.04 0.29
(0.96, 1.28) (0.98, 1.10) (0.16, 4.14) (1.59, 16.7) (2.22, 96.3) (0.73, 5.71) (0.04, 2.40)
0.16 0.20 0.80 0.006 0.005 0.18 0.25
1.21 1.05 0.50 7.54 6.62 1.66 0.24
(1.00, 1.47) (0.97, 1.13) (0.08, 3.10) (1.97, 28.8) (0.81, 53.9) (0.54, 5.08) (0.03, 2.07)
0.05 0.25 0.45 0.003 0.08 0.37 0.19
Absolute ventricular volume measurements Left ventricular stroke volume Right ventricular stroke volume Left ejection fraction Right ejection fraction Left cardiac output Right cardiac output
1.02 1.00 0.92 0.97 1.09 0.91
(1.00, 1.05) (0.98, 1.01) (0.85, 0.99) (0.91, 1.03) (0.81, 1.47) (0.78, 1.07)
0.07 0.71 0.03 0.30 0.57 0.25
1.01 0.99 0.95 0.99 0.96 0.87
(0.99, 1.04) (0.98, 1.01) (0.87, 1.03) (0.93, 1.05) (0.69, 1.33) (0.72, 1.05)
0.37 0.43 0.19 0.72 0.80 0.15
Great vessel flow Net forward flow aorta Net forward flow mpa Pulmonary regurgitation volume Pulmonary regurgitation volume %
1.03 1.03 0.99 0.97
(1.00, 1.06) (1.00, 1.06) (0.97, 1.01) (0.94, 1.00)
0.04 0.04 0.15 0.04
1.02 1.02 0.99 0.98
(0.99, 1.05) (0.99, 1.05) (0.97, 1.01) (0.95, 1.01)
0.25 0.26 0.22 0.11
Age at correction, per year Time since correction, per year PA VSD Male Body surface area (BSA), per m2 Right aortic arch Aberrant neck vessels
138
M. Dennis et al. / International Journal of Cardiology 177 (2014) 136–138
should be taken into account when determining the timing of pulmonary valve replacement in repaired ToF. It is acknowledged that our study maybe influenced by selection and survivor bias with only “survivors” referred to our tertiary referral centre being studied. In our own review of unexpected deaths of adult with ToF, none were attributable to aortic disease after comprehensive postmortem examination [10]. In conclusion our study adds to the growing body of research that identifies that, whilst aortic root dilatation in patients with repaired tetralogy of Fallot does occur, the risk of serious complications including aortic regurgitation and aortic dissection is low. The optimal timing and need for intervention on a dilated aortic root in these patients is still not clear. It also confirms that male sex is the only consistent significant factor contributing to aortic root dilatation and should be taken into account in surveillance of these patients. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] Niwa K, Siu SC, Webb GD, Gatzoulis MA. Progressive aortic root dilatation in adults late after repair of tetralogy of Fallot. Circulation 2002;106:1374–8.
[2] Chong WY, Wong WH, Chiu CS, Cheung YF. Aortic root dilation and aortic elastic properties in children after repair of tetralogy of Fallot. Am J Cardiol 2006;97:905–9. [3] Mongeon FP, Gurvitz MZ, Broberg CS, Aboulhosn J, Opotowsky AR, Kay JD, et al. Aortic root dilatation in adults with surgically repaired tetralogy of Fallot, a multi center cross-sectional study. Circulation 2013;127:172–9. [4] Chowdhury UK, Mishra AK, Ray R, Kalaivani M, Reddy SM, Venugopal P. Histopathologic changes in ascending aorta and risk factors related to histopathologic conditions and aortic dilatation in patients with tetralogy of Fallot. J Thorac Cardiovasc Surg 2008;135:69–77. [5] Senzaki H, Iwamoto Y, Ishido H, Matsunaga T, Taketazu M, Kobayashi T, et al. Arterial haemodynamics in patients after repair of tetralogy of Fallot: influence on left ventricular after load and aortic dilatation. Heart 2008;94:70–4. [6] Devereux RB, de Simone G, Arnett DK, Best LG, Boerwinkle E, Howard BV, et al. Normal limits in relation to age, body size and gender of two-dimensional echocardiographic aortic root dimensions in persons ≥15 years of age. Am J Cardiol 2012; 110:1189–94. [7] Verheught CL, Uiterwaal CS. Gender and outcome in congenital heart disease. Circulation 2008;118:26–32. [8] Rossi P, Frances Y, Kingwell B, Ahimastos A. Gender differences in artery wall biomechanical properties throughout life. J Hypertens 2011;29:1023–33. [9] Niwa K. Aortic root dilatation in tetralogy of Fallot long-term after repair — histology of the aorta in tetralogy of Fallot: evidence of intrinsic aortopathy. Int J Cardiol 2005; 103:117–9. [10] O'Meagher S, Choudhary P, Duflou J, Puranik R, Celermajer D. Causes of death in tetralogy of Fallot in adults — an autopsy study. Int J Cardiol 2013;168(2013):1547–8.
